Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

Severe Sepsis Mimicking Primary Nonfunction Following Liver Transplantation: Normothermic Machine Perfusion Is a Potential Environment for Bacterial Overgrowth and Transmission From Donor to Recipient. A Case Report.

Primary nonfunction (PNF) in the early postoperative period following liver transplantation is fatal if not managed appropriately with early retransplantation. Severe early allograft dysfunction can mimic PNF. The identification of treatable causative factors such as sepsis, hepatic artery, or portal vein thrombosis is essential to distinguish it from PNF, and their early management may avoid the need for retransplantation. In this article, we describe a case of sepsis-induced severe liver dysfunction from a contaminated graft perfused with normothermic machine perfusion (NMP), which presented in a manner similar to PNF. The implications of graft contamination are poorly described. To our knowledge, this is the first report of bacterial contamination of a graft that underwent NMP and subsequently caused severe sepsis in the recipient. The conditions created with NMP may be optimal for certain micro-organisms to thrive. The role of the liver in the immune system is complex as it provides an essential barrier to enterically derived portal venous pathogens and produces numerous acute phase proteins that augment the systemic immune response. Additionally, the liver is also known to restrain harmful and excessive systemic immune responses such as those that occur with the sepsis syndrome. The relationship between bacterial graft contamination, sepsis, and graft dysfunction may be multidirectional.

Long-term follow-up of endoscopic Histoacryl glue injection for the management of gastric variceal bleeding.

BACKGROUND: Variceal bleeding is an acute medical emergency with high mortality. Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding is more severe and more difficult to control. The optimal therapy for gastric variceal bleeding remains unclear although endoscopic injection of N-Butyl-2-Cyanoacrylate (Histoacryl) glue is often used. However, its long-term efficacy is poorly described. We studied the immediate and long-term effects of Histoacryl glue injection as treatment for bleeding gastric varices in a large UK hospital. METHOD: Endoscopy records and case notes were used to identify patients receiving Histoacryl injection for gastric variceal bleeding over a 4-year period. RESULTS: Thirty-one patients received Histoacryl for gastric variceal bleeding. Seventy-four per cent patients had alcohol-related liver disease and 61% of cirrhotics were Childs Pugh grade B or C. Fifty-eight per cent were actively bleeding during the procedure with 100% haemostasis rates achieved. Two patients developed pyrexia within 24 h of injection settling with antibiotics. No other complications were encountered. Mean overall follow-up was 35 months, with mean follow-up of survivors 57 months. Forty-eight per cent patients had endoscopic ultrasound assessment of varices during follow-up with no effect on rebleeding rates. Thirteen per cent required subsequent transjugular intrahepatic portosystemic shunt placement. Gastric variceal rebleeding rate was 10% at 1 year and 16% in total. One- and two-year mortality was 23% and 35%, respectively. CONCLUSION: Endoscopic injection of Histoacryl glue appears to be a safe and effective treatment for gastric variceal bleeding. Further data are required to compare it with other therapies in this situation.

Immune-mediated and chronic inflammatory disease in people with sarcoidosis: disease associations in a large UK database.

BACKGROUND: Sarcoidosis is a multi-system disorder characterised by non-caseating granulomas. Coexistence of sarcoidosis with immune-mediated and chronic inflammatory diseases has been described in case series. However, the coexistence of two different diseases in individuals can occur by chance, even if each of the diseases is rare. AIM: To determine whether sarcoidosis necessitating hospital admission or day-case care coexists with a range of immune-mediated and chronic inflammatory diseases more commonly than expected by chance. DESIGN: Analysis of an epidemiological database of hospital admission and day-case statistics, spanning 30 years. RESULTS: 1510 patients with sarcoidosis were identified (mean age 44 years, median follow-up 19 years) who had been admitted to hospital or day-case care. Significant associations in the sarcoidosis cohort were identified with systemic lupus erythematosus (odds ratio (OR) 8.3; 95% CI 2.7 to 19.4), autoimmune chronic hepatitis (OR 6.7; 95% CI 1.8 to 17.1), multiple sclerosis (OR 3.3; 95% CI 1.7 to 5.6), coeliac disease (OR 3.1; 95% CI 1.01 to 7.3), thyrotoxicosis (OR 2.5; 95% CI 1.4 to 4.0), myxoedema (OR 2.2; 95% CI 1.2 to 3.7) and ulcerative colitis (OR 2.1; 95% CI 1.1 to 3.7). Weaker associations were found for diabetes mellitus with a first admission aged 30-49 years (OR 2.9; 95% CI 2.1 to 4.0) or age >50 (OR 1.7; 95% CI 1.2 to 2.3), but not for people age <30. No significant association with Crohn's disease (OR 1.52; 95% CI 0.61 to 3.14) or primary biliary cirrhosis (OR 3.75; 95% CI 0.77 to 11.0),was found. When all immune-mediated and chronic inflammatory diseases for which associations were sought were combined, the overall rate ratio associated with sarcoidosis was 2.2 (95% CI 1.9 to 2.6). CONCLUSION: This study adds epidemiological evidence to information from clinical reports that there is a connection between sarcoidosis and other immune-mediated and chronic inflammatory diseases.